Adding Acetazolamide to AtoOxy in OSA Not More Effective Than AtoOxy Alone

Atomoxetine plus oxybutynin (AtoOxy) decreased obstructive sleep apnea (OSA) severity by about 50% and acetazolamide decreased OSA severity by about one-third, but the treatments combined had no additional effect vs AtoOxy alone, according study findings published in Thorax.

The randomized, cross-over trial evaluated the effect of AtoOxy plus acetazolamide (triple therapy) before bedtime compared with AtoOxy alone (dual therapy) in patients with moderate to severe OSA.

A total of 19 patients with suspected or diagnosed OSA, aged 18 to 79 years, were enrolled in the study from January 2020 to March 2021. Participants completed a baseline overnight polysomnographic study and then 4 treatment studies 1 week apart in a cross-over design. The primary outcome analysis compared the effects of AtoOxy plus acetazolamide vs AtoOxy alone, and each intervention also was compared with placebo. The effects on Apnea-Hypopnea Index (AHI) were quantified with the percentage decrease from baseline.

Participants completed 3 days of treatment before outcomes assessment. They received half doses of the 3 interventions on the first day for each intervention, with a 4-day washout following each treatment period. Dosing included atomoxetine 80 mg, oxybutynin 5 mg, and acetazolamide 500 mg. The patients had a median age of 45 (interquartile range, 34-51) years, and 16 were men.

AtoOxy plus acetazolamide did not reduce AHI by a greater amount vs AtoOxy alone (difference in change from baseline [%baseline]: +2; 95% CI, −11 to 18; P =.8). Each active intervention reduced the AHI compared with placebo.

AHI was decreased with AtoOxy (−49%baseline; 95% CI, −62 to –33; P =3×10⁻⁶), AtoOxy plus acetazolamide (−47%baseline; 95% CI, −61 to 31; P =8×10⁻⁶), and acetazolamide (−34%baseline; 95% CI, 14 – 50; P =.002), compared with placebo. AtoOxy appeared to lower the AHI by a greater amount vs acetazolamide (−15%baseline; 95% CI, −35, 1; P =.068), but it was not significant.

AtoOxy plus acetazolamide did not reduce hypoxic burden by a greater amount compared with AtoOxy alone (+13%baseline; 95% CI, −5 to 39; P =.18). A decrease in hypoxic burden occurred for AtoOxy (−58%baseline; 95% CI, −71 to –37), with AtoOxy plus acetazolamide (−45%baseline; 95% CI, −63 to –18), and with acetazolamide (−37%baseline; 95% CI, −58 to 5), compared with placebo. AtoOxy was associated with a greater decrease in hypoxic burden compared with acetazolamide (−21%baseline; 95% CI, −53 to 0.4; P =.045).

For arousal index, AtoOxy plus acetazolamide had no greater effect vs AtoOxy alone (−1%baseline; 95% CI, −9 to 7; P =.8). Compared with placebo, a decrease was observed in arousal index with AtoOxy (−15%baseline; 95% CI, −23 to 6), with AtoOxy plus acetazolamide (−16%baseline; 95% CI, −24 to 7), and with acetazolamide (−11%baseline; 95% CI, −20 to 2). AtoOxy had a similar decrease in arousal index vs acetazolamide (−4%baseline; 95% CI, −13 to –5; P =.4).

A nonsignificant but potentially clinically important increase (4 mm Hg) in systolic blood pressure occurred with AtoOxy vs placebo.

Limitations include the short therapy duration and potential for carry-over effects with the cross-over design. Also, the population was relatively young and healthy.

“These findings suggest that the upper airway muscle and breathing stability causes of sleep apnea are more closely overlapping than previously appreciated,” the investigators stated.

Disclosure: The study was a jointly initiated project sponsored by Apnimed. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on Pulmonology Advisor